Blood Glucose Levels In Mice Research Articles

Uptake of the Plant Agriculture-Used Antibiotics Oxytetracycline and Streptomycin by Cherry Radish─Effect on Plant Microbiome and the Potential Health Risk.

Antibiotics are used to control certain bacterial diseases in plant agriculture. Understanding antibiotic uptake by edible vegetables after application and associated risks on plant microbiome and human health is critical. In this study, oxytetracycline and streptomycin, the two most commonly used antibiotics in plant agriculture, were applied to cherry radish via continuous soil drenching to study their translocations into plant tissues, influence on radish microbiome, and the potential health risk to mice. The results demonstrated that oxytetracycline induced hormesis in radish plants and both antibiotics were translocated into the leaves, fruits, and roots of radishes from the soil, with significantly higher plant uptake of streptomycin than oxytetracycline. Interestingly, the proportion of culturable oxytetracycline or streptomycin-resistant bacteria in the antibiotic-accumulated radish tissues was significantly higher than that in the antibiotic-free radish tissues, although both bacterial and fungal communities in different radish tissues were not affected by the accumulated antibiotics, demonstrating that antibiotic application could enrich antibiotic resistance in the plant microbiome. Feeding mice with antibiotics-accumulated radish tissues did not show significant effects on the weight and blood glucose levels of mice. Overall, this study provides important insights into the risk of using antibiotics in plant agriculture.

Acute PDE4 Inhibition Induces a Transient Increase in Blood Glucose in Mice.

cAMP-phosphodiesterase 4 (PDE4) inhibitors are currently approved for the treatment of inflammatory diseases. There is interest in expanding the therapeutic application of PDE4 inhibitors to metabolic disorders, as their chronic application induces weight loss in patients and animals and improves glucose handling in mouse models of obesity and diabetes. Unexpectedly, we have found that acute PDE4 inhibitor treatment induces a temporary increase, rather than a decrease, in blood glucose levels in mice. Blood glucose levels in postprandial mice increase rapidly upon drug injection, reaching a maximum after ~45 min, and returning to baseline within ~4 h. This transient blood glucose spike is replicated by several structurally distinct PDE4 inhibitors, suggesting that it is a class effect of PDE4 inhibitors. PDE4 inhibitor treatment does not reduce serum insulin levels, and the subsequent injection of insulin potently reduces PDE4 inhibitor-induced blood glucose levels, suggesting that the glycemic effects of PDE4 inhibition are independent of changes in insulin secretion and/or sensitivity. Conversely, PDE4 inhibitors induce a rapid reduction in skeletal muscle glycogen levels and potently inhibit the uptake of 2-deoxyglucose into muscle tissues. This suggests that reduced glucose uptake into muscle tissue is a significant contributor to the transient glycemic effects of PDE4 inhibitors in mice.

Uji Efektivitas Ekstrak Umbi Bawang Putih (Allium Sativum l) terhadap Kadar Glukosa Darah Mencit (Mus Musculus) yang Diinduksi Aloksan

This study aims to test the effectiveness of garlic bulbs on alloxan-induced blood glucose levels in mice. The method used is an actual experimental pretest-posttest control group design. The study revealed that garlic extract could reduce blood glucose levels in mice (p 0.05). The most doses of garlic extract that reduced blood glucose levels in diabetic mice were 6 mg/200 g BW and 12 mg/200 g BW. In conclusion, garlic extract significantly reduced blood glucose levels in diabetic mice when administered at 6 mg/200 g BW and 12 mg/200 g BW.
 
 Keywords: Allin, Allisin, Anti Diabetes, Garlic

Extract of Calyces from Physalis peruviana Reduces Insulin Resistance and Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Diabetes mellitus is a metabolic disorder mainly characterized by obesity, hyperglycemia, altered lipid profile, oxidative stress, and vascular compromise. Physalis peruviana is a plant used in traditional Colombian medicine for its known activities of glucose regulation. This study aimed to evaluate the anti-diabetic activity of the butanol fraction from an extract of Physalis peruviana calyces in two doses (50 mg/kg and 100 mg/kg) in induced type 2 diabetic mice. Blood glucose levels were evaluated once a week, demonstrating that a dose of 100 mg/kg resulted in greater regulation of blood glucose levels in mice throughout the experiment. The same overall result was found for the oral glucose tolerance test (OGTT) and the homeostatic model assessment for insulin resistance (HOMA- IR). The lipid profile exhibited improvement compared to the non-treated group, a dose of 100 mg/kg having greater protection against oxidative stress (catalase, superoxide dismutase, and malondialdehyde levels). Histopathological findings in several tissues showed structure preservation in most of the animals treated. The butanol fraction from Physalis peruviana at 100 mg/kg showed beneficial results in improving hyperglycemia, lipidemia, and oxidative stress status, and can therefore be considered a beneficial coadjuvant in the therapy of diabetes mellitus.

Antihyperglycemic activity of nanoemulsion of brown algae (Sargassum sp.). Ethanol extract in glucose tolerance test in male mice

Nanoemulsion technology has been widely developed and applied to extracts of natural materials to enhance bioavailability and medicinal effects. This study aimed to determine the effectiveness of the Sargassum sp. ethanol extract nanoemulsions as an antihyperglycemic agent against fasting blood glucose levels in mice. The nanoemulsion formulation used Sargassum sp. extract and some additional ingredients, including chitosan, sodium tripolyphosphate, and tween 80. The antihyperglycemic test consisted of four groups, which were randomly selected. Treatment group (I) was given a nanoemulsion base without algae extract with a volume of 0.2mL/20gramBW; treatment group (II) was given glibenclamide at a dose of 0.52mg/20gramBW in 0.5% carboxymethylcellulose sodium (NaCMC) suspension with a volume of 0.2mL/20gramBW; treatment group (III) was given Sargassum sp. ethanol extract at a dose of 0.66mg/20 gramBW in 0.5% Na CMC suspension with a volume of 0.2mL/20gramBW; the treatment group (IV) was given formula of nanoemulsions of ethanol extract Sargassum sp with a volume of 0.2mL/20gramBW equivalent to a dose concentration Sargassum sp. ethanol extract of 0.66mg/20gramBW. The size of the nanoemulsion particles of the Sargassum sp. extract was 341.5-296.5nm with a zeta potential of 19.4-16.9mv. Treatment group (II) had the same antihyperglycemic effect as treatment group (IV). In contrast, treatment groups (I) and (III) had a relatively lower antihyperglycemic effect. This suggests that the Sargassum sp. extract nanoemulsion formula can be used as an alternative antihyperglycemic agent.

N-Caffeoyltryptophan enhances adipogenic differentiation in preadipocytes and improves glucose tolerance in mice

Coffee consumption has been shown to reduce the risk of developing type 2 diabetes mellitus (T2DM) in humans; however, the exact mechanism is not completely understood. Here, we demonstrate that N-caffeoyltryptophan (CTP), an ingredient of coffee, enhances adipogenic differentiation and promotes glucose uptake into adipocytes. CTP increased lipid accumulation and adipogenic markers (PPARγ, C/EBPα, and FABP4) expression in mouse 3T3-L1 preadipocyte cell lines and primary preadipocytes. In addition, CTP promoted glucose uptake in 3T3-L1 cells. In the oral glucose tolerance test, daily administration of CTP (30 mg/kg/day, i.p.) for a week reduced blood glucose levels in mice. In 3T3-L1 cells, adipogenic differentiation and increased adipogenic markers expression induced by CTP were inhibited by U0126, a selective MEK1/2 inhibitor. Furthermore, mRNA induction of Pparg by CTP was abrogated in SIRT1 siRNA-transfected 3T3-L1 cells. These results suggest the involvement of the MEK/ERK signaling and SIRT1 in the mechanism of adipogenic function of CTP. Taken together, CTP might contribute to the reduction in postprandial glycemia and a subsequent reduction in onset risk for T2DM.

Electroacupuncture reduces blood glucose by regulating intestinal flora in type 2 diabetic mice.

BackgroundThe development of diabetes is closely related to the gut microbiota in recent studies, which can be influenced by intestinal motility. A few studies report that electroacupuncture (EA) can lower blood glucose. EA can promote colonic motility and influence gut microbes. In this study, we explored the effect of the EA on blood glucose level in mice with type 2 diabetes (T2D) and its mechanism.MethodsThe T2D mice model, fecal microbiota transplantation mice model, and KitW/Wv mice model （Point mutation of mouse W locus encoding kit gene）were used to investigate the effect of EA on blood glucose as well as the mechanism; The blood glucose and insulin resistance level and the intestinal flora were evaluated. The level of intestinal junction protein, inflammatory cytokines in the serum, interstitial cells of Cajal content, and colonic motility were detected. Lastly, the IKKβ/NF‐κB‐JNK‐IRS‐1‐AKT pathway was explored.ResultsEA lowered the blood glucose level, altered the gut microbiota, and promoted colonic motility in T2D mice. EA‐altered microbiota decreased the blood glucose level and insulin resistance in the antibiotics‐treated diabetic mice. EA increased tight junction protein, lowered inflammatory factors, and regulated the IKKβ/NF‐κB‐JNK‐IRS‐1‐AKT pathway in the liver and muscles. EA could not reduce the blood glucose and regulated gut microbiota in the KitW/Wv mice model.ConclusionsEA promoted intestinal motility to regulate the intestinal flora, thereby reducing the level of systemic inflammation, and ultimately lowering the blood glucose by the IKKβ/NF‐κB‐JNK‐IRS‐1‐AKT signal pathway.

The Effect of Petai (Parkia Speciosa Hassk) Seed Extract and Glimepiride on Blood Sugar Levels Of Alloxan-Induced Mice (Mus Musculus)

Diabetes mellitus is a metabolic disease characterized by hyperglycemia as a result of insulin deficiency in the body, ineffective insulin function, or both. Glimepiride is a third generation of oral hypoglycemic drug (OHO) that has a lower risk of hypoglycemia and weight gain compared to the first generation of sulfonylurea. Petai plant (Parkia speciosa Hassk) is one of the medicinal plants that has been known to be efficacious as antioxidant and anti-diabetic. This study aimed to discover the effect of administering the seeds of petai (Parkia speciosa Hassk) on blood glucose levels in mice induced by alloxan. This experimental study used 42 mice divided into 5 groups, they were K- (a standard diet), K+ (alloxan 175 mg/kgBB), control treatments P1 and P2 with doses of 300 mg/kgBB and 400 mg/kgBB of petai seed extract, and control treatment P3 with Glimepiride 0.0026/20g. This research was conducted at Pharmacology Laboratory of the Faculty of Pharmacy and Biochemistry of the Faculty of Medicine, Andalas University. Blood sugar levels were measured by the colorimetric method using vitalab micro spectrophotometer (Microlab 300). The results of the Kruskal-Wallis test on the blood sugar levels of mice with the administration of petai seed extract at a dose of 300mg/KgBB with a mean decrease in blood sugar levels of 85.48±5.32 mg/dl and on the blood sugar levels of mice with the administration of Glimepiride 0.0026mg/20gBB with a mean decrease in blood sugar levels of 88.73±9.95 mg/dl for 7 days did not show a statistically significant difference in the Post Hoc Test with Mann-Whitney (p = 0.423) with a mean difference of reduction of 3.25mg/dl. The conclusion of this study is that the petai seed extract has the same effective effect as Glimepiride to reduce blood sugar levels in alloxan-induced mice.

TonEBP in Myeloid Cells Promotes Obesity-Induced Insulin Resistance and Inflammation Through Adipose Tissue Remodeling.

The phenotypic and functional plasticity of adipose tissue macrophages (ATMs) during obesity plays a crucial role in orchestration of adipose and systemic inflammation. Tonicity-responsive enhancer binding protein (TonEBP) (also called NFAT5) is a stress protein that mediates cellular responses to a range of metabolic insults. Here, we show that myeloid cell-specific TonEBP depletion reduced inflammation and insulin resistance in mice with high-fat diet-induced obesity but did not affect adiposity. This phenotype was associated with a reduced accumulation and a reduced proinflammatory phenotype of metabolically activated macrophages, decreased expression of inflammatory factors related to insulin resistance, and enhanced insulin sensitivity. TonEBP expression was elevated in the ATMs of obese mice, and Sp1 was identified as a central regulator of TonEBP induction. TonEBP depletion in macrophages decreased induction of insulin resistance-related genes and promoted induction of insulin sensitivity-related genes under obesity-mimicking conditions and thereby improved insulin signaling and glucose uptake in adipocytes. mRNA expression of TonEBP in peripheral blood mononuclear cells was positively correlated with blood glucose levels in mice and humans. These findings suggest that TonEBP in macrophages promotes obesity-associated systemic insulin resistance and inflammation, and downregulation of TonEBP may induce a healthy metabolic state during obesity.

Uygur type 2 diabetes patient fecal microbiota transplantation disrupts blood glucose and bile acid levels by changing the ability of the intestinal flora to metabolize bile acids in C57BL/6 mice

BackgroundOur epidemiological study showed that the intestinal flora of Uygur T2DM patients differed from that of normal glucose-tolerant people. However, whether the Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and the mechanism behind has not been reported. This study was designed to explore whether Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and its mechanism.MethodsThe normal diet and high fat diet group consisted of C57BL/6 mice orally administered 0.2 mL sterile normal saline. For the MT (microbiota transplantation) intervention groups, C57BL/6 mice received oral 0.2 mL faecal microorganisms from Uygur T2DM. All mice were treated daily for 8 weeks and Blood glucose levels of mice were detected. Mice faecal DNA samples were sequenced and quantified using 16S rDNA gene sequencing. Then we detected the ability of the intestinal flora to metabolize bile acids (BAs) through co-culture of fecal bacteria and BAs. BA levels in plasma were determined by UPLC-MS. Further BA receptors and glucagon-like peptide-1 (GLP-1) expression levels were determined with RT-q PCR and western blotting.ResultsMT impaired insulin and oral glucose tolerance. Deoxycholic acid increased and tauro-β-muricholic acid and the non-12-OH BA:12-OH BA ratio decreased in plasma. MT improved the ability of intestinal flora to produce deoxycholic acid. Besides, the vitamin D receptor in the liver and ileum and GLP-1 in the ileum decreased significantly.ConclusionsUygur T2DM fecal microbiota transplantation disrupts glucose metabolism by changing the ability of intestinal flora to metabolize BAs and the BAs/GLP-1 pathway.

Pengujian Efek Hipoglikemik Fraksi Petroleum Eter dan Etil Asetat Daun Dandang Gendis (Clinacanthus nutans (Burm. F.) Lindau)

The investigation had been done about hypoglycaemic effect from Clinachanthus nutans (Burm f.) Lindau extract, which in petroleum ether extract and ethyl acetate extract, that used Glucose Method Tolerance for Mice. The extract of Clinachanthus nutans (Burm f.) Lindau leave was carried out by masseration and using ethanol 80% as solvent, and gradually fractination for ethanol extract with petroleum ether and ethyl acetate solvent. Further, the glucose tolerance had been done for petroleum ether fraction and ethyl acetate. The mice was fasting during 17 hours and the blood glucose level and weight of mice was measured and given the 50% glucose liquid with dose 4 mg/kg bw. After 30 minutes the blood glucose level can be measure again. Divided the mice to 6 group, Group I: control (CMC 0,5% dose 1 % bw); Group II until Group V given the petroleum ether fraction and ethyl acetate fraction with dose 15, 30, 45 dan 60 mg/kg bw; Group VI: given the Glibenclamid suspension dose 1 mg/kg bw as equal. Fixed blood glucose level of mice after 60, 90, 120, 150 and 180 minutes to have use of glucometer (EZ Smart). The result showed that petroleum ether extract doesn’t have hypoglycaemic effect, but in dose 45 and 60 mg/kg bw has given hypoglycaemic effect which to get near Glibenclamid suspension in dose 1 mg/ kg bw with blood glucose level decrease 0,05 (ɑ=0,05).

Epigallocatechin-3-Gallate (EGCG) as a potential therapeutic against cardiovascular disease risk in mice

Objective: Research is focused on cardiovascular disease (CVD). CVD is the leading cause of death in the world and remains one of the major diseases strongly affected by diet and sedentary lifestyle. CVD is a class of diseases relates to the heart and or blood vessels that include, stroke, heart failure, hypertension, coronary artery disease, peripheral artery disease, and atherosclerosis caused partly due to dyslipidemia. The aim of this study was to determine the potential effect of epigallacatechin-3-gallate (EGCG) on blood lipid and glucose profiles in mice exposed to conditions that lead to CVD. Groups of male mice were subjected to different diet (standard fat diet, high fat diet and low-fat diet), exercise (voluntary, chronic and sedentary lifestyle) and EGCG supplementation. EGCG powder was dissolved in 4 ml of drinking water to deliver a daily dose of 30 mg/kg. Mice were anesthetized with isoflurane (Abbott, Cham, Switzerland) 2% (v/v) in a 20% O2 and 80% air mixture by inhalation in a closed container, then euthanized by manual cervical dislocation and were put on the animal's bed for a blood sample from the cardiac puncture. Blood was collected for lipid profiles and glucose analysis. The data was analyzed using a multi variate approach including one-way analysis of variance test (one-way ANOVA), Tukey –Kramer multiple comparison test and pairwise correlation analysis was used to determine the significance between control and treated groups. Results: The mice subjected to high-fat diet (Anova p-value = 0.00) and sedentary lifestyle (Anova p-value = 0.00) showed elevated levels for total cholesterol, low density lipoprotein’s cholesterol, triglycerides and glucose. EGCG supplementation in mice undergoing high fat diet and sedentary lifestyle resulted in a significant reduction in the lipid profiles and blood glucose (Anova p-value = 0.00). Our study showed that a high fat diet and a sedentary lifestyle predispose to hyperlipidemia and high blood glucose levels in mice and also proved that EGCG fed to hyperlipidemia mice reduces lipid levels in blood.

Antioxidant Potential of White Turi Stem (Sesbania grandiflora) in Reducing Malondialdehyde (MDA) and Blood Glucose Levels in Type 2 Diabetes Mellitus Model Mice

Type 2 Diabetes Mellitus triggers hyperglycaemia conditions resulting in oxidative stress which is characterized by increased production of Reactive Oxygen Species (ROS) inducing in cell damage, resulting in lipid peroxidation which decomposes in the blood into Malondialdehyde (MDA). The use of natural antioxidants is believed to be safer and more effective in the long term. One of the plants that has a strong antioxidant content and activity is the White Turi Plant (Sesbania grandiflora). This study aimed to examine the antioxidant activity of white turi (Sesbania grandiflora) stem extract in reducing MDA and blood sugar levels in Type 2 DM model mice. A quasi-experimental method with an in vivo design was used in this study. A sample of 30 hyperglycaemic mice was divided into 5 groups: group K- was given aquadest and standard feed, group K+ was given glibenclamide 0.013 mg/20gBW, group I was given extract at a dose of 2.8 mg/20gBW, group II was given extract at a dose of 5, 6 mg/20gBW and group III was given extract at a dose of 11.2 mg/20gBW. At the end of the study, blood glucose and MDA levels will be measured as a biomarker of oxidative stress. Repeated measurement Anova and One-way Anova test was used in this study, it was found that white turi (Sesbania grandiflora) stem extract at a dose of 2.8 mg/gBW had an effect on decreasing blood glucose levels in mice. Moreover, based on the results of the MDA level test, it showed that there was an effect of white turi stem extract on reducing MDA levels in the blood of mice. In conclusion, white turi stem (Sesbania grandiflora) has the potential to reduce MDA and blood sugar levels in Type-2 DM model mice. Keywords: [White Turi Stem (Sesbania grandiflora), Malondialdehyde, Blood Glucose, Reactive Oxygen Species, Diabetes Mellitus Type2] .

Chemical and Pharmacological Profiling of Wrightia coccinea (Roxb. Ex Hornem.) Sims Focusing Antioxidant, Cytotoxic, Antidiarrheal, Hypoglycemic, and Analgesic Properties.

The aim of the study was to conduct phytochemical and pharmacological investigations of Wrightia coccinea (Roxb. ex Hornem.) Sims via several in vitro, in vivo, and in silico models. A total of four compounds were identified and isolated from the methanol extract of the bark and the methanol extract of the seed pulp of W. coccinea through successive chromatographic techniques and were characterized as 3β-acetyloxy-olean-12-en-28-ol (1), wrightiadione (2), 22β-hydroxylupeol (3), and β-sitosterol (4) by spectroscopic analysis. The aqueous fraction of the bark and chloroform fraction of the fruits provided the most potent antioxidant capacity (IC50 = 7.22 and 4.5 µg/mL, respectively) in DPPH free radical scavenging assay compared with the standard ascorbic acid (IC50 = 17.45 µg/mL). The methanol bark extract and the methanol fruit coat extract exerted anti-diarrheal activity by inhibiting 74.55 ± 0.67% and 77.78 ± 1.5% (mean ± SEM) of the diarrheal episode in mice, respectively, after four hours of loading the samples. In the hypoglycemic test, the methanol bark extract and the methanol fruit coat extract (400 mg/kg) produced a significant (p < 0.05) reduction in the blood glucose level in mice. Both doses of the plant extracts (200 mg/kg and 400 mg/kg) used in the study induced a significant (p < 0.05) increase in pain reaction time. The in vitro and in vivo findings were supported by the computational studies. The isolated compounds exhibited higher binding affinity compared with the standard drugs towards the active binding sites of glutathione reductase, epidermal growth factor receptor (EGFR), kappa opioid receptor, glucose transporter 3 (GLUT 3), Mu opioid receptor, and cyclooxygenase 2 (COX-2) proteins due to their potent antioxidant, cytotoxic, anti-diarrheal, hypoglycemic, and central and peripheral analgesic properties, respectively. The current findings concluded that W. coccinea might be a potential natural source for managing oxidative stress, diarrhea, hyperglycemia, and pain. Further studies are warranted for extensively phytochemical screening and establishing exact mechanisms of action.

EFFECTIVENESS OF NONI EXTRACT CAPSULES (Morinda (Morinda citrifolia L.) ON REDUCING BLOOD GLUCOSE LEVELS OF MICE (Mus musculus L.)

Empirical and research result proved that chemical contents of noni plant have medical benefits. Former research showed that noni fruit extract has antihyperglicemic effect. This research was aimed to determines the effectivity of noni fuit extract (Morinda citrofolia L.) capsule to lowering mice blood glucose level. This research was used glucose induced hyperglicemic mice with treatment groups such as: negative control group, noni fruit extractt capsule dose 1, and noni fruit extract capsule dose 2. Noni fruit extract capsule dose 1 treated group showed 40,7±10,8 mg/dl blood glucose level drop and 38,7±16,6 mg/dl drop for dose 2 treated group. The conclusion of this research is noni fruit extract capsule lowering mice blood glucose level.

Effect of palm sap (Arenga pinnata) on blood glucose levels of mice (Mus musculus) alloxan-induced diabetic

Abstract. Liputo SM, Lamondo D, Solang M. 2021. Effect of palm sap (Arenga pinnata) on blood glucose levels of mice (Mus musculus) alloxan-induced diabetic. Asian J Nat Prod Biochem 20: 11-15. This study aims to determine the effect of palm sap (Arenga pinnata (Wurmb) Merr.) in reducing blood glucose levels in alloxan-induced diabetic mice (Mus musculus Linnaeus, 1758). Twenty-five mice aged 2-3 months were grouped into a negative control group, a positive control group and a palm sap group (0.2 mL, 0.4 mL, and 0.6 mL). The result showed that the palm sap with a dose of 0.4 mL was the most significant in reducing blood glucose levels. This study concluded that the administration of palm sap affected decreasing blood glucose levels (p &lt;0.05).

Investigation on the differentially expressed circular RNAs in myocardium of mice with diabetic cardiomyopathy

Objective: To identify the differentially expressed circular RNA (circRNA) in the myocardium of diabetic cardiomyopathy (DCM) mice, and analyze their possible biological functions and related regulatory network. Methods: C57BL/6 mice, aged 8 weeks, and weighing were 21-27 g. Eight mice were selected as the control group and 15 mice were selected as the experimental group. The diabetic mice model was established by intraperitoneal injection of streptozotocin in the experimental group. One week after injection, the fasting blood glucose level of mice was measured, and 12 diabetic mice were included in the final experimental group. All mice were fed for 12 weeks under the same laboratory conditions. The cardiac structure and function were detected by echocardiography. Diabetic mice with the left ventricular ejection fraction less than 60% and the E/A less than 1.6 were selected as DCM group (n=3). Mice in DCM group and control group were then sacrificed under deep anesthesia. RNA was extracted from myocardial tissue. High-throughput RNA sequencing technology was used to sequence and identify the RNA in the myocardial tissue of DCM group and normal control group, and the difference was analyzed by DeSeq2. The analysis results were verified at the tissue level by RT-qPCR, and the differential circRNA were analyzed by GO and KEGG pathway analysis. The differentially expressed circRNA-microRNA(miRNA) interaction was predicted by the miRNA target gene prediction software. Results: A total of 63 differentially expressed circRNAs were found in the myocardium of DCM mice. The results of RT-qPCR showed that the tissue level expression of 8 differentially expressed circRNAs was consistent with the sequencing results, of which 7 were up-regulated and 1 was down-regulated. KEGG pathway analysis showed that the up-regulated circRNAs was mainly related to AMPK signal pathway and intercellular adhesion junction pathway, and the down-regulated circRNA was mainly related to cardiomyopathy. Go analysis showed that the up-regulated circRNA was mainly related to the binding process of ions, proteins, kinases and other factors in terms of molecular function, and was involved in regulating the intracellular structure, especially the composition of organelles in terms of cell components. The functional analysis of molecular function and cell components showed that the up-regulated circRNA were related to the cell component origin, recruitment and tissue, and thus participated in the regulation of cell biological process. The down regulated circRNA was related to catalytic activity in terms of molecular function, protein kinase binding process, transferase and calmodulin activity, and was closely related to the components of contractile fibers and the composition of myofibrils. These differentially expressed circRNAs were also related to biological processes such as lysine peptide modification, sarcomere composition, myofibril assembly, morphological development of myocardial tissue, myocardial hypertrophy and so on. Conclusions: In this study, we detected the novel differentially expressed circRNAs in the myocardium of DCM mice, and bioinformatics analysis confirmed that these circRNAs are related to oxidative stress, fibrosis and death of cardiomyocytes, and finally participate in the pathophysiological process of DCM.

Withdrawn: SGLT2 inhibitor ipragliflozin poses a low risk of hypoglycaemia owing to its blood glucose-dependent urinary glucose excretion mechanism in mice.

Sodium-glucose cotransporter (SGLT) 2 inhibitors, which inhibit renal reabsorption of glucose and stimulate urinary glucose excretion, have been proposed as useful drugs for treating diabetes. This study examined the effects of the SGLT2 inhibitor ipragliflozin on blood glucose-dependent urinary glucose excretion in mice. To investigate the antihyperglycemic effects of ipragliflozin, several oral glucose tolerance tests (glucose load: 1-4 g/kg) were performed. Ipragliflozin significantly suppressed the increases in blood glucose levels concomitant with urinary glucose excretion. To investigate the risk of hypoglycemia, the effects of ipragliflozin were examined under fasting conditions in mice that prefasted for various time periods (0-24 h). Ipragliflozin significantly decreased blood glucose levels in mice that had prefasted for 0 or 6 h (non-hypoglycemic conditions), but not in mice that had prefasted for 12 h or more (hypoglycemic conditions). These ipragliflozin-induced hypoglycemic and urinary glucose excretion effects were well correlated with blood glucose levels. These results suggest that ipragliflozin-induced increases in urinary glucose excretion and accompanying hypoglycemic effects were caused by blood glucose-dependent mechanisms. Thus, ipragliflozin may be a useful antidiabetic agent that achieves ideal blood glucose control in diabetic patients with little risk of hypoglycemia.

Tyrosine Hydroxylase‐Positive Neurons in the Hypothalamic Paraventricular Nucleus Modulate Blood Glucose Levels in Mice

Tyrosine hydroxylase (TH)‐positive neurons in the paraventricular nucleus of the hypothalamus (PVN), termed THPVN neurons, have emerged as key metabolic regulators. Recent studies showed that THPVN neurons are mostly Gamma‐aminobutyric acid (GABA)ergic and/or dopaminergic. Previous results from our laboratory indicate that THPVN neurons project to brainstem autonomic regulatory nuclei, such as nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM). However, it is not known if THPVN neurons play a role in blood glucose regulation. We hypothesize that THPVN neurons are key regulators of blood glucose. To test our hypothesis, we used adeno‐associated virus serotype 2 (AAV2)‐mediated Cre‐recombinase driven by a rat TH promoter (AAV2‐TH‐Cre), in combination with chemogenetic approach (Designer Receptors Exclusively Activated by Designer Drugs, DREADD) to activate or inhibit THPVN neurons and continuously monitored blood glucose levels using telemetry system. hM3Dq‐LoxP (excitatory‐DREADD) and hM4Di‐LoxP (inhibitory‐DREADD) mice, 10‐14 weeks old, were bilaterally microinjected with AAV2‐TH‐Cre into the PVN. One month following AAV injection, mice were implanted with telemetry glucose transmitters (HD‐XG, DSI) to monitor blood glucose (BG) levels. To activate or inhibit THPVN neuronal activity, Clozapine‐N‐oxide (CNO, 1 mg/Kg) or vehicle were administered (i.p.) and BG was monitored by telemetry. To examine the functional role of THPVN neurons at baseline and avoid the influence of feeding on blood glucose levels, mice were fasted for 2 hours and fasting was maintained throughout the experiment. We found that activation of THPVN neurons by CNO in hM3Dq‐LoxP mice did not alter baseline blood glucose (n=5); on the other hand, inhibition of THPVN neurons by CNO in hM4Di‐LoxP mice increased baseline blood glucose levels compared with vehicle only in male mice (Male: ΔBG: 31.6 ± 8.6 mg/dL vs. 11.0 ± 6.7 mg/dL, n=4, p=0.03; Female: ΔBG: 11.0 ± 7.4 mg/dL vs. 7.3 ± 5.9 mg/dL, n=4, p=0.16). To study the functional role of THPVN neurons on whole body glucose handling, mice were fasted overnight and simultaneously injected with glucose (1 g/Kg) and either vehicle or CNO. We found that activation of THPVN neurons by CNO improved glucose clearance after glucose overload when compared with vehicle (AUC: 3133.0±109.0 vs. 6021.0±102.0, p&lt;0.0001, n=3) in hM3Dq‐LoxP mice. In summary, our data suggest that THPVN neurons negatively regulate blood glucose possibly by their GABAergic input to downstream neural circuits. We conclude that THPVN neurons play a functional role in the regulation of glucose homeostasis; while the mechanisms remain to be determined.

Anti-aging potential of cookies from sea grapes in mice fed on cholesterol- and fat-enriched diet: in vitro with in vivo study

This study determines the effect of cookies made from sea grapes (Caulerpa racemosa) on PGC-1α, total cholesterol, and blood glucose levels on mice fed with a Cholesterol- and Fat-Enriched Diet (CFED). The antioxidant activity, tyrosinase inhibition, α-glucosidase, and α-amylase inhibition is also analyzed in order to assess the in vitro anti-aging potential of sea grapes cookies. Forty male Mus muscullus albino mice weighing 20 g–30 g were used and randomly distributed into four groups of ten animals each. Group A served as a normal control (given a standard dry pellet diet), Group B was given CFED only, and mice in Groups C and D were given CFED with 100 mg and 200 mg/20 g body weight of sea grapes cookies, respectively for 4 weeks. In vitro study shows that the percentage of inhibition activity of antioxidant, L-Tyrosine, L-Dopa, α-glucosidase, and α-amylase inhibition were 45.65 ± 1.50, 8.95 ± 0.06, 21.31 ± 0.98, 77.12 ± 4.67 and 70.94 ± 0.98, respectively. This study found that group D had better activity in lowering blood glucose than group C (p < 0.0001). In addition, although there was not found significant difference between groups C and D in blood cholesterol reduction and PGC-1α (p = 0.1482), both groups experienced the same effect in total cholesterol reduction and PGC-1α in mice (significantly, p < 0001). Thus, we conclude that sea grapes cookies are proven to improve PGC-1α, total cholesterol, and blood glucose levels in mice fed with CFED. Hence, sea grapes cookies is a potential anti-aging novel-functional food.